Phase I/II Study of Decitabine and All-Trans Retinoic Acid (Tretinoin) for Patients With Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of myelodysplastic cells, either by killing the cells or by stopping them from dividing. Tretinoin and decitabine may help myelodysplastic cells become more like normal cells, and to grow and spread more slowly. Giving decitabine together with tretinoin may be an effective treatment for myelodysplastic syndromes.
PURPOSE: This phase I/II trial is studying the side effects and best dose of tretinoin when given together with decitabine in treating patients with myelodysplastic syndromes.
详细描述
OBJECTIVES:
Primary
- Determine the hematologic and nonhematologic toxicities of decitabine in combination with tretinoin in patients with myelodysplastic syndromes. (Phase I)
- Determine the maximum tolerated dose of tretinoin when administered with decitabine in these patients. (Phase I)
- Determine the clinical remission rate (complete and partial remission) in patients treated with this regimen. (Phase II)
- Determine the rate of hematologic improvement in these patients. (Phase II)
Secondary
- Determine the efficacy of this regimen, in terms of improved bone marrow function, by monitoring frequency of transfusion, bleeding, and infection, as well as changes in bone marrow morphology and cytogenetics in these patients.
- Assess differentiation by morphology and flow cytometry and apoptosis by flow cytometry in patients treated with this regimen.
- Determine if gene expression changes in these patients are induced by this regimen.
- Determine the efficacy of this regimen, in terms of inducing demethylation of specific genes, in these patients.
- Correlate clinical response with gene expression, demethylation of specific genes, and flow cytometric indicators of differentiation and apoptosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: decitabine (Drug)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: tretinoin (Drug)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: DNA methylation analysis (Genetic)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: cytogenetic analysis (Genetic)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: microarray analysis (Genetic)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: flow cytometry (Other)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
Decitabine and All-Trans Retonoic Acid (Tretinoin)
干预措施: immunohistochemistry staining method (Other)
结局指标
主要结局
Number of Participants Evaluated for Hematologic and Nonhematologic Toxicities as Measured by NCI CTC v2.0
时间窗: Up to 1 year
Maximum Tolerated Dose of Tretinoin When Administered With Decitabine as Determined by NCI CTC v2.0 (Phase II)
时间窗: Up to 1 year
Overall Response Rate
时间窗: Up to 1 year
Overall Response Rate is defined as Complete Response + Partial Response
Rate of Hematologic Improvement as Measured by Responding Cell Lines (Erythroid, Platelet, and Neutrophil Response) (Phase II)
时间窗: After each cycle
次要结局
- Change in Bone Marrow Function as Measured by Frequency of Transfusion, Bleeding, and Infection as Well as Changes in Bone Marrow Morphology and Cytogenetics(After each cycle)
- Differentiation as Measured by Morphology and Flow Cytometry and Apoptosis as Measured by Flow Cytometry(After each cycle)
- Gene Expression Changes as Measured by Affymetrix Gene Profiling Studies(After each cycle)
- Demethylation of Specific Genes as Measured by Gene Promoter Methylation Studies(After each cycle)
- Correlation of Clinical Response, With Gene Expression, Demethylation of Specific Genes, and Flow Cytometric Indicators of Differentiation and Apoptosis(After each cycle)